|Dr. rer. nat. Alvar Prönneke|
|Ort||Kreuzbergring 40, 37075 Göttingen|
Neocortical GABAergic interneurons expressing vasoactive intestinal polypeptide (VIP) contribute to sensory processing,sensorimotor integration, and behavioral control. In contrast to other major subpopulations of GABAergic interneurons, VIPneurons show a remarkable diversity. Studying morphological and electrophysiological properties of VIP cells, we found apeculiar group of neurons in layer II/III of mouse primary somatosensory (barrel) cortex, which showed a highly dynamicburst firing behavior at resting membrane potential that switched to tonic mode at depolarized membrane potentials.Furthermore, we demonstrate that burst firing depends on T-type calcium channels. The burst-tonic switch could beinduced by acetylcholine (ACh) and serotonin. ACh mediated a depolarization via nicotinic receptors whereas serotoninevoked a biphasic depolarization via ionotropic and metabotropic receptors in 48% of the population and a purelymonophasic depolarization via metabotropic receptors in the remaining cells. These data disclose an electrophysiologicallydefined subpopulation of VIP neurons that via neuromodulator-induced changes in firing behavior is likely to regulate thestate of cortical circuits in a profound manner.
Neocortical GABAergic interneurons have a profound impact on cortical circuitry and its information processing capacity. Distinct subgroups of inhibitory interneurons can be distinguished by molecular markers, such as parvalbumin, somatostatin, and vasoactive intestinal polypeptide (VIP). Among these, VIP-expressing interneurons sparked a substantial interest since these neurons seem to operate disinhibitory circuit motifs found in all major neocortical areas. Several of these recent studies used transgenic Vip-ires-cre mice to specifically target the population of VIP-expressing interneurons. This makes it necessary to elucidate in detail the sensitivity and specificity of Cre expression for VIP neurons in these animals. Thus, we quantitatively compared endogenous tdTomato with Vip fluorescence in situ hybridization and αVIP immunohistochemistry in the barrel cortex of VIPcre/tdTomato mice in a layer-specific manner. We show that VIPcre/tdTomato mice are highly sensitive and specific for the entire population of VIP-expressing neurons. In the barrel cortex, approximately 13% of all GABAergic neurons are VIP expressing. Most VIP neurons are found in layer II/III (∼60%), whereas approximately 40% are found in the other layers of the barrel cortex. Layer II/III VIP neurons are significantly different from VIP neurons in layers IV-VI in several morphological and membrane properties, which suggest layer-dependent differences in functionality.
The neocortex is regarded as the brain structure responsible for mediating higher brain functions, like conscious perception of sensory signals, learning and memory or programming of goal-directed behavior. Cortical circuits that enable these functions are formed by, first, a larger population of excitatory so-called principal cells (i.e., glutamatergic pyramidal cells; ca. 80–85 %), which issue long-distance projections, in addition to local recurrent collaterals, which form the major part of local cortical excitatory circuits. A second, smaller population of inhibitory also called local or short-axoned interneurons (i.e., GABAergic neurons; ca. 15–20 %), however, contribute heavily to intracortical microcircuits too. They can be subdivided by their location in specific areas, layers, or columns, which possess specific input–output relationships, but also in terms of morphology, electrophysiology, molecular expression profiles, and subcellular target specificity. Here it is proposed that, at present, in the rodent neocortex this population of GABAergic neurons can be reasonably divided into six different types, mainly due to their unique axonal patterns and subcellular target specificity: (i) axo-axonic cells, (ii) basket cells, (iii) Martinotti cells, (iv) bipolar/bitufted cells, (v) neurogliaform cells, and (vi) projection neurons. These different types of GABAergic neurons strongly govern the working of cortical circuits for meaningful behavior by feed-forward and feedback inhibition as well as disinhibition. Thus, they keep excitation in check, perform gain modulation, and open temporal or spatial windows for input control or output generation.